Despite the high prevalence and morbidity of severe obesity among adolescents in the United States, few rigorous studies of hypocaloric dietary therapy have been done. Hypotheses regarding the interactions of glucose and protein metabolism have been based on levels of hormones and substrates rather than direct measurements and correlations of rate of glucose production (Ra) and protein catabolism. The optimal diet for weight reduction in any age group is that diet which maximizes the utilization of fat and minimizes the loss of protein. In our previous study we compared 1.5 gm protein plus 1.0 gm glucose/kg ideal body weight (IBW)/day (P + G) with an isonitrogenous diet made isocaloric by the addition of fat (P + F). Because fat may not spare protein under hypocaloric dietary conditions, we will extend these studies by comparing P + G with 2.5 gm protein/kg IBW/day. Twenty-two adolescents will consume each diet in a crossover fashion for two 28 day periods. Protein intake will be based on IBW determined by measuring total body water with H2-18-O. This will be measured with 6,6-d2-glucose. Protein catabolism will be measured by N-balance and a-15N-lysine turnover. Our previous studies of a-15N-lysine will be further validated by comparison with studies of 1-13C-leucine. In addition, measurement of 13C enrichment of a-ketoisocaproic acid in samples collected during the 1-13C-leucine infusion will allow us to account for the intracellular dilution of isotope by unlabeled amino acid. Comparisons of 3-13C-alanine incorporation into glucose will be used to measure the relative contribution of protein catabolism to gluconeogenesis. Changes in body composition on the two diets will be measured by repeated determinations of total body water with H2-18-O. Rates of fat oxidation will be measured by open circuit indirect calorimetry. Our results will provide further information essential to rational dietary therapy for morbidly obese adolescents, and will yield new insights into the mechanisms by which these diets exert their metabolic effects.